Clinacin Solution

Description

Clinacin Solution: is a palatable formulation intended for oral administration to dogs and cats. Clinacin Solution contains: Active Ingredient: each mL contains 25 mg Clindamycin (as clindamycin hydrochloride) which is the hydrated salt of clindamycin. Clindamycin is a semi-synthetic antibiotic produced by a 7 (S) - chloro-substitution of the 7 (R) -hydroxyl group of lincomycin, a naturally-produced antibiotic produced by Streptomyces lincolnensis var. lincolnensis.

Therapeutic Classification:

Actions:

Site and Mode of Action: Clindamycin is an inhibitor of protein synthesis in the bacterial cell. The site of binding appears to be in the 50S sub-unit of the ribosome. Binding occurs to the soluble RNA fraction of certain ribosomes, thereby inhibiting the binding of amino acids to those ribosomes. Clindamycin differs from cell wall inhibitors in that it causes irreversible modification of the protein-synthesizing sub-cellular elements at the ribosomal level.

Microbiology: The following clindamycin in vitro data are available but their clinical significance is unknown. Clindamycin has been shown to have in vitro activity against isolates of the following organisms: Aerobic gram positive cocci, including: Staphylococcusaureus (penicillinase and non-penicillinase producing strains), Staphylococcus intermedius, Staphylococcus simulans, Staphylococcus epidermidis, streptococci (except S. faecalis) and pneumococci.

Clostridia: Most C. perfringens are susceptible, but other species, e.g., C. sporogenes and C. tertium are frequently resistant to clindamycin.

Mycoplasma species: Most Mycoplasma species are susceptible to clindamycin.

Clindamycin and erythromycin show parallel resistance. Partial cross resistance has been demonstrated between clindamycin, erythromycin and macrolide antibiotics.

Clinacin Solution Indications

Dogs

For treatment of infected wounds, abscesses and dental infections caused by or associated with Staphylococcus spp., Streptococcus spp., Bacteroides spp., Fusobacteriumnecrophorum and Clostridiumperfringens and osteomyelitis caused by Staphylococcusaureus.

Cats

For treatment of infected wounds, abscesses and dental infections caused by or associated with Staphylococcus aureus, Staphylococcus intermedius,Streptococcus spp., Clostridiumperfringens and Bacteroides fragilis.

Treatment with Clinacin Solution may be continued up to a maximum of 14 days if clinical judgment indicates. Treatment of acute infections should not be continued for more than 3 to 4 days if no clinical response to therapy is seen.

Contraindications

Clinacin Solution is contraindicated in animals with a history of hypersensitivity to preparations containing clindamycin or lincomycin. In the event of a hypersensitivity reaction following the administration of this drug, immediate appropriate therapy should be instituted.

Cautions:

1. The use of Clinacin Solution occasionally results in overgrowth of non-susceptible organisms such as clostridia and yeasts. Should super infections occur, appropriate measures should be taken as indicated by the clinical situation.

2. Because of potential adverse gastrointestinal effects, do not administer to rabbits, hamsters, guinea pigs, horses, chinchillas or ruminating animals.

3. While high dose studies in rats suggest that clindamycin is not a teratogen and did not significantly affect the reproductive performance of males or females, safety in gestating bitches and queens or breeding male dogs and cats has not been established.

4. Clindamycin hydrochloride has been shown to have neuromuscular blocking properties that may enhance the action of other neuromuscular blocking agents. Therefore, Clinacin Solution should be used with caution in animals receiving such agents. Partial cross resistance has been demonstrated between clindamycin, erythromycin and macrolide antibiotics.

5. During prolonged therapy of one month or greater, periodic liver and kidney function tests and blood counts should be performed. Patients with severe renal and/or very severe hepatic disturbances accompanied by severe metabolic aberrations should be dosed with caution and should be monitored by serum examination during high-dose clindamycin therapy.

Therapeutically effective serum levels of clindamycin hydrochloride can be maintained by oral dosing at the rate of 5.5 mg/kg every 12 hours. Dogs orally dosed with clindamycin hydrochloride at 5.5 mg/kg every 12 hours during a 72 hour dosing regimen continuously maintained antibacterial serum levels of the drug. This same study revealed that average peak serum concentrations occurred 1 hour and 15 minutes after dosing. The biological half-life for clindamycin hydrochloride in dog serum is approximately 5 hours. There was no bioactivity accumulation after a regimen of multiple oral doses.

Cats Serum Levels:

Therapeutically effective serum levels of clindamycin hydrochloride can be maintained by oral dosing at the rate of 11 - 22 mg/kg body weight once every 24 hours. The average peak serum concentration of clindamycin hydrochloride occurs about 1 hour after oral administration. The biological half-life of clindamycin hydrochloride in feline serum is approximately 7.5 hours. No bioactivity accumulation occurs after multiple oral doses.

Extensive studies of the metabolism and excretion of clindamycin hydrochloride administered orally in animals and humans have shown that unchanged drug and bioactive and bioinactive metabolites are excreted in urine and feces. Almost all of the bioactivity detected in serum after the administration of clindamycin hydrochloride is due to the parent molecule (clindamycin). Urine bioactivity, however, reflects a mixture of clindamycin and active metabolites, especially N-demethyl clindamycin and clindamycin sulfoxide.

One year oral toxicity studies in rats and dogs at doses of 30, 100 and 300 mg/kg/day have shown clindamycin hydrochloride to be well tolerated. Differences did not occur in the parameters evaluated to assess toxicity when comparing groups of treated animals with contemporary controls. Rats administered clindamycin hydrochloride at 600 mg/kg/day for 6 months tolerated the drug well; however, dogs orally dosed at 600 mg/kg/day vomited, had anorexia, and subsequently lost weight. Safety studies in gestating bitches or breeding males have not been run, however, teratology and reproductive studies in male and female rats at 50 mg/kg and higher showed no drug related effects.

Clindamycin hydrochloride was well tolerated with little evidence of toxicity in domestic shorthair cats when administered orally at 10x the minimum recommended therapeutic daily dose of 11 mg/kg for 15 days, at doses up to 5x the minimum recommended therapeutic dose for 42 days. Gastrointestinal tract upset (soft feces to diarrhea) occurred in control and treated cats with emesis occurring at doses 3x or greater than the minimum recommended therapeutic dose (11 mg/kg/day). Lymphocytic inflammation of the gallbladder was noted in a greater number of treated cats at the 110 mg/kg/day dose level than for control cats. No other effects were noted. Safety in gestating queens or breeding male cats has not been established.

In Vitro Susceptibility Testing

Susceptibility tests should be done on samples collected prior to initiation of therapy with Clinacin Solution. Clindamycin susceptibility testing is performed by using Cleocin® Susceptibility Disks (clindamycin 2 mcg) and Cleocin® Susceptibility Powder 20 mg. A standardized disk testing procedure1 is recommended for determining susceptibility of aerobic bacteria to clindamycin. A description is contained in the Cleocin® Susceptibility Disk insert. Using this method the laboratory can designate isolates as resistant, intermediate, or susceptible. Tube or agar dilution methods may be used for aerobic and anaerobic bacteria. When the directions in the Cleocin® Susceptibility Powder insert are followed, a MIC (minimal inhibitory concentration) of 1.6 mcg/mL may be considered susceptible; MICs of 1.6 to 4.8 mcg/mL may be considered intermediate and MICs greater than 4.8 mcg/mL may be considered resistant.

Every effort has been made to ensure the accuracy of the Clinacin Solution information published above. However, it remains the responsibility of the readers to familiarize themselves with the product information contained on the Canadian product label or package insert.